The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole

1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800  mg sulphamethoxazole and 160  mg trimethoprim) alone or 1  h after either fluconazole (150  mg) or ketoconazole (200  mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24  h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N₄-acetyl sulphamethoxazole, or sulphamethoxazole N₁-glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points.     

THE INTERACTION BETWEEN ENALAPRILAT AND SELECTED α-ADRENOCEPTOR ANTAGONISTS IN ISOLATED RAT TAIL ARTERIES

1. Isolated perfused rat tail artery preparations were used to investigate the effects of the angiotensin converting enzyme inhibitor enalaprilat on the actions of a series of α-adrenoceptor antagonists. The agonist used was phenylephrine. 2. Enalaprilat (1 μmol/L) potentiated the competitive α₁-adrenoceptor antagonist actions of phentolamine (10–100 nmol/L) and yohimbine (0.3–3.0 μmol/L) as well as the non-competitive antagonist action of phenoxybenzamine (50–100 pmol/L). 3. The competitive α₁-adrenoceptor antagonist action of prazosin (1–10 nmol/L) was not affected by enalaprilat. 4. For the competitive α₁-adrenoceptor antagonists, including prazosin, there appeared to be an inverse relationship between antagonist potency and the extent of potentiation by enalaprilat. 5. The results support the hypothesis and angiotensin II modulates vascular smooth muscle α₁-adrenoceptor function.     

胎盘组织液氨基酸的含量测定及层析鉴别

本文采用层析法进行鉴定,用氨基酸分析仪测氨基酸的含量,为胎盘组织液的质量标准提供可靠依据。本法准确率为99%。     

Spatial frequency content of the Cardiff and related acuity tests

In the Cardiff acuity test, simple pictures on an otherwise neutral grey card are defined by borders consisting of a relatively broad white band flanked by black bands each half the width of the white band. Higher levels of acuity correspond to the ability to detect figures defined by narrower borders, the figure size remaining constant. It is sometimes implied that the acuity limit corresponding to each card can be equated with different levels of grating resolution, the total width of the border corresponding to the overall grating period. It is shown that although the spatial frequency spectra of the Cardiff figures, like those of other vanishing optotypes, lack very low-frequency components, they have a complex two-dimensional form. The figures have wide spatial bandwidth and no well-defined discrete frequency components. As a result, the relationship between measured Cardiff and grating acuity will vary somewhat, depending upon the particular optical, neural or other deficits of the individual being tested.     

Behavioral models in mice. implication of the alpha noradrenergic system

1. The mechanism of action of drugs might change according to the test used. Several noradrenergic drugs were tested in order to understand their implication in the mobility tests.

2. It was found that clonidine, an Alpha 2 agonist, acted differently according to the tast used. It provoked sedation in spontaneous activity test, and anti-immobility effects in the other tests.

3. Tall suspension test is able to show the double acting of clonidine.

4. Idazoxan might act either as an alpha 2 antagonist or as partial alpha 2 agonist. TST shown the unexpected partial alpha agonist effect of the molecule.

5. Forced swimming test is more specific for predicting antidepressant activity than tail suspension test which is close to a spontaneous activity model.     

Spectral characteristics of early receptor potential in congenital red-green color blindness

The spectral response curve (amplitude versus wavelength) of the R₂ of the early receptor potential (ERP) was studied in normal, protan, and deutan subjects. The R₂ amplitude peaked at 520nm in most normal subjects. The R₂ at long wavelengths was smaller than normal in protans and larger than normal in deutans when the maximum amplitudes were normalized to 100% at the peak. The ratio of the R₂ amplitude at 460 nm to that at 600 nm clearly differed between protans and deutans. The ERP and the rapid off-response, which is mainly due to the cessation of the late receptor potential, were recorded in the same subjects. The ratio of the sensitivity of the rapid off-response at 500 nm to that at 600 nm was correlated with the ratio of the R₂ amplitude at 460 nm to that at 600nm (correlation coefficient, 0.823, p < 0.001). This study, in conjunction with our previous study, indicates that the abnormality is in the outer segments of the cones in protans and deutans.     

Effect of etodolac on the prostaglandin concentrations in the kidney of the normal rat

The effect of acute and subchronic dosing with etodolac on the renal PGE₂ and 6-keto-PGF_1α concentrations in the normal rat were studied. Etodolac and other nonsteroidal antiinflammatory drugs (NSAIDs) were administered orally, at equieffective antiinflammatory doses, to normal rats either as a single dose or as seven daily doses. Whole kidney prostaglandin (PG) concentrations were measured. In the acute study, etodolac (3 mg/kg) did not significantly lower the PGE₂ levels for up to 4 hr postdosing. In contrast, naproxen (3 mg/kg) and piroxicam (0.5 mg/kg) significantly decreased the PGE₂ levels to about 20% and 60% of control, respectively. Similar reductions in 6-keto-PGF_1α concentrations were observed. In the subchronic study, etodolac (3 mg/kg/day) did not lower either PGF₂ or 6-keto-PGF_1α concentrations whereas naproxen (3 mg/kg/day), piroxicam (0.5 mg/kg/day), indomethacin (1 mg/kg/day), and aspirin (300 mg/kg/day) significantlydecreased both PGs. In both studies, the effect of etodolac was significantly different from that of the NSAIDs. It is concluded that etodolac possesses only a very weak capacity to lower renal PGs, and therefore is unlikely to cause any renal complications related to PG biosynthesis inhibition.     

Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate-induced irritant contact dermatitis

OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti-irritative effect of PoCo was evaluated with a visual score and quantified by non-invasive bioengineering methods, namely chromametry and transepidermal water loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient; German pharmacopoeia) were tested in a 4-day repetitive irritation test using SLS. RESULTS: A statistically significant anti-inflammatory activity was observed for PoCo by all three methods when applied in parallel to the induction period of ICD. Application of PoCo after induction of ICD once a day for 5 days, starting just at the end of 4 days, was without any effect. CONCLUSION: An anti-inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by repeated SLS test could be observed and quantified by three independent, non-invasive biophysical assessment parameters. This effect can be explained by its influence on pro-inflammatory enzymes, namely phospholipase A2.